A crew of Purdue College scientists led by Shihuan Kuang has acquired a $2.5 million grant from the Nationwide Institutes of Well being to outline the position of lipid droplets in muscle stem cell perform, a examine with implications in each people and livestock.
“Lipid droplets are vital as a regulatory part of the stem cell. The content material of lipid droplets makes the stem cell perform higher or worse,” stated Kuang, Most cancers Heart Chair in Stem Cell Biology and a professor of animal sciences in Purdue’s Faculty of Agriculture.
The human angle will give attention to muscle-related illness, growing older and harm. The livestock side will delve into animal development to boost meat manufacturing, high quality and style. Working with Kuang on the challenge are Christina Ferreira, a developmental biologist with coaching in analytical chemistry within the Bindley Bioscience Heart; James Markworth, assistant professor of animal sciences; and Chi Zhang, assistant professor of chemistry within the Faculty of Science.
The grant follows a examine that Kuang and eight Purdue co-authors revealed within the journal Cell Experiences final yr exhibiting how fats performs an sudden position within the destiny of muscle stem cells.
“We all know that when you perturb lipid droplets, the cells don’t do properly,” Kuang stated. “The query now could be what do the lipid droplets do within the cell? Do they complement power to the cells? Or do the lipid droplets maybe secrete sure forms of molecules that regulate cell perform?”
Individuals typically consider lipids as dangerous as a result of they accumulate inside the physique as fats tissue, Markworth stated. The NIH challenge, nonetheless, will discover the potential constructive position that lipids could play as vital signaling molecules in muscle.
“Proper now, we do not actually know what forms of lipids are present in these droplets,” he stated.
Markworth is very within the position of lipid metabolites – often called bioactive lipid mediators – in muscle biology. Are dietary important omega-3 or omega-6 (wholesome unsaturated fat) discovered inside lipid droplets, for instance?
“Does the kind of fats that they comprise affect their position? And do their numerous downstream metabolites play totally different roles in figuring out stem cell destiny?” he stated.
Prior to now, scientists considered the droplets as inert storage containers, “like a rubbish can,” Kuang stated. Studying extra about how lipid droplets affect stem cells may result in their manipulation to restore muscle harm extra quickly or to heal muscle illness, he stated.
The work has relevance to sarcopenia – widespread, age-related muscle atrophy – in addition to metabolic illnesses that have an effect on the muscle, resembling weight problems and diabetes. The therapy of main genetic muscle illnesses, resembling Duchenne muscular dystrophy, and of extra widespread exercise-induced and traumatic muscle harm additionally may benefit.
From an animal science perspective, “lipid droplets are discovered within the muscle of livestock species, the meat that we eat,” Markworth stated. “The composition of lipid droplets within the meat could have an effect on each the style of the meat and its dietary worth to the human weight loss plan. If we are able to manipulate lipid within the muscle, we may probably improve meat high quality.”
Markworth joined the Division of Animal Sciences school in 2021. His collaborations with Kuang point out the division’s heightened give attention to primary muscle analysis.
“My lab want to hyperlink the position of lipids and their downstream bioactive molecules in muscle again to way of life, diet, weight loss plan and train behaviors,” Markworth stated. “If we perceive what lipids are vital inside the cells, their position and the way they perform, we are able to manipulate this simply by what sort of lipids we eat.”
Lipid droplets are amongst many various kinds of cogs within the mobile equipment. On the Bindley Heart’s Metabolite Profiling Facility, Ferreira chemically analyzes the lipids and different small molecules associated to the metabolic regulation of the muscle stem cells that the crew is learning.
“When cells change their lipid composition, they alter their roles in metabolism,” she stated.
Ferreira makes use of an array of extremely delicate methods, together with two developed by Purdue’s Graham Cooks, the Henry Bohn Hass Distinguished Professor of Analytical Chemistry, to profile the metabolism of stem cells and to chemically display screen their related lipid droplets.
“Stem cells are very uncommon. They seem in small numbers,” Ferreira stated. Lipid droplets, in the meantime, are tough to chemically analyze due to their nanoscale dimension. Hundreds of them may lay side-by-side throughout the width of a single human hair.
Zhang provides Raman spectroscopy to the challenge. With this imaging methodology, he measures the compositions of lipids in reside cells. Raman imaging exploits the way in which that molecular vibrations hyperlink to mild beams to measure chemical compositions. He additionally has developed an imaging approach that enables the crew to observe the lipid droplets because the stem cells convert to muscle cells and different cell varieties.
“We’re a gaggle for creating instruments. We hope that our instruments can be utilized by biologists,” Zhang stated. “Discovering functions is all the time the motivation we’ve.”
His group at the moment is designing a device that may take pictures of muscle cells whereas additionally controlling their destiny as they differentiate. The group is also testing easy methods to exactly goal a laser solely on lipid droplets to see if manipulating the droplets may change the stem-cell differentiation course of.
Whereas Purdue’s NIH examine will give attention to muscle, it has potential implications for stem cells all through the physique, together with neural stem cells.
“Lipid droplets may play an analogous position in different tissue stem cell varieties that aren’t studied but,” Kuang stated.
